Grant: Doctoral: Vanier Canada Graduate Scholarships

Major depressive disorder (MDD) is a medical condition defined by various symptoms, including overwhelming sadness, reoccurring thoughts of death, etc., persisting for more than 2 weeks. WHO¿s Burden of Disease Statistics (2002) ranked depression as the most burdening disease in Canada, measured by Disability Adjusted Life Years. The socioeconomic consequence of MDD is tremendous and therefore, much time and effort has been invested in an attempt to elucidate the aetiology of the disease. It has been generally accepted that MDD is an outcome of both genetic and environmental influences. However, despite enormous efforts, no conclusive genetic or environmental marker has been identified thus far. One of the difficulties faced by the traditional research approach is that MDD is a complex disease which exhibits heritability patterns that do not follow Mendel¿s laws. MDD exhibits discordance between monozygotic twins, sexual dimorphism, parent-of-origin effect, and fluctuating disease course - none of which are consistent with DNA sequence-based disease mechanisms. Epigenetic refers to the regulation of gene expression that are not based on DNA sequence, but rather, controlled by heritable and reversible changes to the DNA (methylation of cytosines) and/or the chromatin structure (modifications of histones). The epigenetic model of major depressive disorder can explain the peculiar characteristics of complex diseases and provide a new interpretation of various non-Mendelian features of MDD. The goal of this study is to understand if and how epigenetic factors are relevant to the aetiological mechanisms of major depressive disorder. This study will be performed on a number of unique samples, which will enable us to interrogate most aspects of MDD using the epigenetic model. Epigenetic markers of MDD may provide new opportunities for the rational design of the next generation of depression drugs, as well as the development of a diagnostic marker for MDD.